Thinning of hair with an intact hairline is the characteristic feature of female pattern hair loss (FPHL).
Miniaturization is the leading cause of thinning in FPHL. It can be because of androgen-dependent and androgen-independent mechanisms.
Differential diagnoses from other causes such as diffuse alopecia areata, and chronic telogen effluvium is needed.
Thorough investigations are required to know the underlying cause and treatment accordingly.
Counseling is a must for the psychological support of the patient.
Minoxidil is the primary treatment for all the grades of FPHL.
Treatment of underlying causes such as PCOS, thyroid disorder, iron deficiency can also play an important role.
Hair Loss in Female
Female pattern hair loss (FPHL) is the most prevalent type of hair loss in females. It has a great psychological impact on the affected women. Onset may be early in the post-pubertal age or maybe late after the age of 40 years nearer to menopause or post-menopause. Approximately half of women over the age of 50 years are affected by FPHL. The main feature of male and female pattern hair loss is the miniaturization of the hair follicle, but it does not progress to total baldness in females because all hairs are not equally affected. The process of miniaturization mainly starts in the central scalp and extends to peripheries with the preservation of anterior hairline. During the early phase of FPHL, there is increased shedding; later on, it stabilizes. A brown halo at the base of the hair exit point from the scalp of affected follicles is the clinical clue to pattern hair loss (peri-pilar sign). Topical minoxidil application is the mainstay of treatment, along with the treatment of other underlying causes.
Fig. A, B Difference in the pattern of female and male hair loss
PATHOGENESIS OF FEMALE HAIR LOSS
Pathogenesis of female hair loss is slightly different from male pattern hair loss and is still not well understood. Hair loss is genetic, but the role of androgens in female hair loss is debatable.
Brich et al have summarized that female pattern hair loss is a multifactorial genetically determined trait that can be due to androgen-dependent and androgen-independent mechanisms. Smith and Wells state that 54% of women with FPHL have first male relatives showing androgenetic alopecia, and 23 % of women with FPHL had female relatives having hair loss. The lack of genetic history of hair loss does not rule out the diagnosis. There is a possibility that early and late FPHL are distinct genetically and that the cause of FPHL is polygenic. Other factors like autoimmunity, hypothyroidism, and prolactin are also associated with FPHL.
Signs of hyperandrogenism may beseen in patients of FPHL despite normal levels of androgen.Hair loss in non-hyperandrogenic women may be due to a high level of response to androgens scalp hair follicles. A woman with hyperandrogenism shows hair loss similar to MPHL. Female androgenetic alopecia(FAGA) is hair loss in females because of androgenetic causes.
In patients with AGA, three enzymes and AR receptors are present in the outer root sheath and dermal papillae of hair follicles. These enzymes are 5α-reductase I, II, and aromatase. Female frontal hair follicles have 40 % lower AR receptor content than that in the male hair follicles. Also, 5α-reductase I and II levels are 3 and 3.5 times less in frontal hair follicles of women. However, aromatase content in frontal hair is six times higher in women.This may, in part, explain the difference in the clinical expression of PHL between men and women.
Aromatase catalyzes testosterone and androstenedione to estrogen, estradiol, and estrone. These metabolites of androgen bind with circulating sex hormone-binding globulin. (SHBG). Thereby the availability of free androgen is reduced. Free testosterone is required for the formation of dihydrotestosterone(DHT). There is an inverse correlation between FPHL and concentration of sex hormone-binding globulins. This concept is supported by evidence that if a woman is given an aromatase inhibitor, there will be female pattern hair loss.
Fig-Pathophysiology of FPHL
Role of hormones (Estrogens) in female pattern hair loss
Healthy development of pubic and axillary hair requires estrogen in females, but its role in scalp hair growth in both sexes is less clearand less studied.
Conversion of androgens to estrogens takes place in the presence of aromatase (e.g., Testosterone into 17β-estradiol and androstenedione into estrone).
Estrogens affect androgen metabolism within dermal papilla cells. They reduce DHT production from testosterone either by direct inhibition of 5α-reductase or through the estrogen-induced conversion of testosterone into weaker steroids.
The role of estrogens as a stimulatory or inhibitory agent to hair growth is controversial. Increased incidence of FPHL after menopausefavours its stimulatory effect.
Prolongation of anagen phase during pregnancy is due to high systemic estrogen whereas the post-partum declinein estrogen levels may be responsible for simultaneous conversion of hair follicles into the telogen phase, resulting in the condition telogen gravidarum.
Aromatase inhibitor therapies result in a decrease in estrogen levels and induce hair loss.
Conversely, estrogens have been shown to inhibit hair growth in murine animal models. An aromatase gene variant associated with higher circulating estrogen levels is known to occur at higher frequencies in women with FPHL compared with unaffected women.
CLASSIFICATION OF FEMALE PATTERN HAIR LOSS
There are three main classifications of female pattern hair loss. Ludwig, Olsen, and Hamilton developed these, and Sinclair also proposed a five-point scale of FPHL. The most commonly used classifications are those of Ludwig and Olsen.
1)Ludwig’s classification of FPHL
Diffuse pattern of hair loss. Three degrees have been described based on hair loss severity and thinning in the superior scalp (vault). The anterior hairline is intact. There is no temporal recession.
2) Olsen Classification (Christmas tree pattern)-
She classified hair loss and thinning in the central part line in the shape of the Christmas tree pattern with frontal accentuation. As the stages advance in severity, the pattern emerges in an endpoint similar to that of Ludwig diffuse pattern.
3)Hamilton Classification of FPHL
The classification is based on a bitemporal recession,which he reported in about 13% of premenopausal and 37% of postmenopausal women resulting in Hamilton types II to IV MPHL patterns.
4)Sinclair also proposed a classification of FPHL that is similar to the Ludwig grading. He described a five patterned scale of hair loss.
Widening of the central partition
Widening of the central partition + thinning of the hair on either side of the central part
Diffuse hair loss along with the hair loss on the top of the scalp
Advanced hair loss.
Female Hair Loss Diagnosis
In the early phase of FPHL, there is an increase in shedding (positive hair pull test), latter this stabilizes. The lack of shedding is due to the post telogen lag phase, delay in the onset of anagen, and reduced overall terminal hairs. During the lag phase, small eraser-sized areas of baldness, termed “focal atrichia,” develop ( described by Olsen)
Miniaturization of affected hair is present but does not progress to baldness as opposed to MPHL. Because all hairs are not affected, and miniaturization is not profound.
FPHL can be associated with chronic telogen effluvium.
In pattern hair loss, there is a brown halo at the base of the hair, as it exits the scalp of the affected follicles. This is known as thePeripilar sign.
Many of these women develop small (2 to 5mm) oval or irregular shaped areas of total alopecia – Lacunae or Lakes.
In some cases of FPHL, there may be decreased density in the temporal, parietal,and occipital regions (unpattern hair loss). These are the donor areas for hair transplantation; therefore, such patients may not be good candidates for hair transplantation.
History 2. Examination 3. Blood test
History – Points to be noted are
Time of onset of hair loss, hair shedding or hair breakage, Relationship of hair loss to any event or any disease, menstrual cycle history, history of hair growth over other parts of the body.
Local Examination – any areas of hair loss, bald patches or thinning, any hair loss or thinning in the occipital region. Any signs in the hair loss area include peripilar sign, focal atrichia, broken hair, erythema, scaling, or atrophy. A hair pull test differentiates between CTE, FPHL and diffuse alopecia areata
Investigations – Routine blood count, thyroid function test, iron profile, hormone level test Dermoscopy, and if needed, skin biopsy.
Blood test for hair loss in Females
• Regular periods
• Irregular periods (not on oral contraceptive pills)
• Morning Sample on day 3-4 of menstrual cycle.
– CBC, TSH, Ferritin, Vitamin D , ANA, Others.
– Regular periods + acne + Hirsutism
– CBC, TSH, Ferritin, Vitamin D, Total testosterone, DHEAS
– CBC, TSH, Ferritin, Vitamin D, LH, FSH, Prolactin, DHEAS, Free testosterone, Total testosterone, androstenedione, 17- hydroxyprogesterone, estradiol
Dermoscopy and Histopathology findings in pattern hair loss-
1. Decrease in terminal hair (increased vellus hair)
2. Decrease in anagen hair (increased telogen hair)
3. Increase in follicular stelae (presence of fibrous track at the place of the terminal hair) ending in superficially located miniaturized follicles.
4. Mild perifollicular lymphocytic infiltrate primarily around the upper follicle.
5. Concentric perifollicular fibrosis may be present.
6. Sebaceous gland remains intact.
Dermoscopy and Histopathology findings of pattern hair loss.
Differential Diagnosis of FPHL
To differentiate chronic telogen effluvium (CTE, the hair pull test is positive all over thescalp, but in patterned hair loss (PHL) hair pull test is positive in the affected area only and negative in the occipital region.
In alopecia areata, both telogen and dystrophic anagen hairsare present, but only telogen hairs in FPHL during the hair pull test.
Common causes of Female Hair Loss
• Female Androgenetic Alopecia (FAGA)
• Telogen effluvium (TE)
• Scarring Alopecia (FFA, CCCA etc.)
• Alopecia Areata
• Others (due to some disease or drug, chemotherapy)
Treatment of Female Hair Loss
Treatment of FPHL depends on the underlying pathology causing hair loss. The therapy includes minoxidil, anti-androgen, corrections of hormonal abnormalities, vitamins, and ferritin correction. Minoxidil is still the mainstay of treatment for FPHL.
Hair loss in females leads to great psychological distress, so counseling is an integral part of the management of hair loss in females.
Individual counseling is the first important step in the treatment of hair loss in females. The cause of hair loss, the need for long term treatment, management of stress, diet modifications are essential points to be included while counseling. Sometimes anxiolytics, and or in severe cases, the psychiatric opinion may help.
The US FDA advised the topical use of 2% minoxidil twice a day over the scalp. The 5 % minoxidil foam preparation once a day is also advisable, which is more acceptable by patients. Skin reactionsare less with foam as compared to the solution. Minoxidil solution contains propylene glycol, which is more irritating than isopropyl alcohol, which is used as a preservative in the foam. 5% minoxidil has more advantages over 2%, but side effects occur more frequently.
1 ml minoxidil solution is applied over the entire dry, non-oily scalp. The solution should not spill over the face or other body areas. For patients who are covering a large area, the amount may need to be increased to 2 or 3 ml. With foam, a palmful will need to cover a large area.
Minoxidil solution is also available in combination with tretinoin, to increase its absorption. Another combination of minoxidil with amenexil is also available. Amenexil reverses perifollicular fibrosis.
Side effects of minoxidil
Contact dermatitis and non-virilizing hypertrichosis are the main side effects. The other is dryness of scalp and deposition of a drug over the scalp and hair shaft. The side effects are more with 5% compared to 2%.
Caution-pregnant women should not use it because of the possibility of neonatal hypertrichosis
If there is associated inflammation or seborrhoea, ketoconazole shampoo should be used.
Oral Minoxidil –
Low dose oral minoxidil 0.25 mg to 2.5 mg (LDOM) is used off label in the treatment of FPHL. It shows comparable or sometimes better improvement in patients with female pattern hair loss to 5% topical minoxidil. It is beneficial for patients who cannot tolerate the side-effects of topical minoxidil ( contact dermatitis). In such patients, long term compliance is better with LDOM as compare to topical minoxidil.
Common side effects of LDOM are hypertrichosis, increased heart rate, lower limb edema, and general malaise. Spironolactone is used to control fluid retention caused by oral minoxidil, but it may increase the incidence of postural hypotension. A study by Sinclair using combination therapy of low dose oral minoxidil 0.25mg and oral spironolactone 25 mg shows that it is safe and effective in the treatment of FPHL. Once-daily oral minoxidil also reduces hair shedding in CTE.
Another study by Juan Jimenez at al; suggests that oral minoxidil in a dose of 2.5 to 5 mg/ day shows better response than 0.25 mg/day with almost the same rate of hypertrichosis and pedal edema.
The author suggests that the use of oral minoxidil in FPHL shall be done with proper evaluation of the patient’s benefit and risk during treatment.
Oral Anti androgen – Cyproterone acetate and spironolactone (androgen receptor blocker) are used to treat hair loss in premenopausal women. But are not approved by USFDA for FPHL treatment.
Caution All premenopausal women taking anti-androgensmust be on oral contraceptive pills (OCP) or contraceptive devices due to the risk of feminization of a male fetus. A few preparations are available, having a combination of anti-androgen and oral contraceptives.
Antiandrogenic oral contraceptive pills are the first line of treatment for females with hair loss secondary to PCOS.
The cyproterone acetate-dose is 50 to 100 mg daily for ten days, along with oral contraceptive pills given in the first half of the menstrual cycle.
Spironolactone-It is an antagonist of aldosterone and an antiandrogenic. It reduces androgen production, widely used for FPHL, but it is off label for FPHL. There can be good results in hair regrowth. It is pregnancy category C and should be given with OCP in premenopausal women. Serum K+ levels should be tested before starting and periodicallywhile using. The dose is 100 to 200 mg daily. Improvement is seen in six months of its use.
Finasteride- The use of finasteride for FPHL is not recommended before menopause, and it’s off label use requires consent and detailed explanation.
Following are conclusions of a few studies done to see the effect of finasteride in women:
The lower dose of 1 mg every day is not sufficient.
A higher dose of 2.5 to 5 mg every day is useful to increase hair growth.
More useful in women with hyperandrogenism.
A Korean study suggests improvements in density and thickness treated with
finasteride 5 mg daily to pre and postmenopausal with normal androgenetic women.
Women with high levels of 5 alpha-reductase will benefitfrom finasteride.
Side effects–occasional headache, menstrual irregularity
Caution: Finasteride is teratogenic, and it is pregnancy category X. A pregnant woman taking it or handling a crushed tablet may have feminization of the fetus. While prescribing to females, informed consent and measures to prevent pregnancy are mandatory. Male partners can take it even if they are planning for a baby.
Finasteride is not useful for senescent alopecia after 65 years of age. There is a reduction in hair length and diameter of the hair shaft that is not dependent on DHT, so they will not respond to a 5-alpha reductase inhibitor.
Dutasteride is a potent teratogenic, contraindicated in childbearing age. Off label use in postmenopausal women shows minimal improvement.
Flutamide is a potent non-steroidal anti-androgen. It is contraindicated in men because of the loss of virilism, and it is hepatotoxic also. It is not licensed for FPHL. It is useful in females with PCOS. The dose is 62.5 mg a day; at this dose, toxicity is rare.
The advantage of nutritional supplementation with amino acids, biotin, zinc, Vit B12, Vit D, Iron, and other micronutrients in any form of hair loss is controversial. Still, studies show the relation between deficiency of serum ferritin, vitamin D, and other nutrients with the increased incidence of TE or FPHL. There are several mechanisms by which iron and vitamin D have possible effects on hair growth. Correcting these nutritional deficiencies, along with the minoxidil application, helps improve hair quality and promote hair growth in females.
Prostaglandins analog Bimatoprost-
Prostaglandin D2 is an essential second messenger involved in hair follicle miniaturization in response to androgen stimulation. The prostaglandin analog bimatoprost is used for glaucoma shows eyelash growth. It is currently under trial for use in androgenetic alopecia.
LLLT or low light laser therapy (now called photobiomodulation) has recently been used to treat female androgenetic alopecia. The US FDA has not approved LLLT for AGA, but it has been cleared for safety for human use. The basic principle of working LLLT is a thermal (cold) cellular photo bio modulation. The light photons are absorbed by intracellular receptors so-called chromophores or photoreceptors. The wavelength needed to have photostimulation ranges from 500 to 1100 mm. Studies show that the wavelengths that enhanced the biostimulation effects and maximum DNA synthesis are 620nm, 670nm, 760nm, and 830 nm, so red or near-infrared light is utilized in LLLT
Effect of LLLT on hair follicles
LLLT stimulates anagen re-entry of telogen hair follicles and prolongs the duration of anagen phase. It increases mitochondrial respiration and cell energy in the form of adenosine triphosphates (ATP) and nitric oxide. LLLT also promotes angiogenesis and reduces cellular inflammation. There is an increase in hair density and diameter and a decrease of hair shedding, resulting in clinical improvement of alopecias.
Many LLLT devices are available commercially, starting from hair comb, brush, a cap for home use, and a hood or helmet type available for hair treatment centers. Frequency of treatment depends on the specification of the device, alternate day, or every day for 15 to 25 mints per sitting. The hair growth results are noticeable after the regular use of LLLT for at least 16 to 24 weeks. The success of LLLT also depends on the characteristics of hair and scalp skin. Good compliance with patients is also a contributory factor.
LLLT is advised as an adjuvant therapy to minoxidil and finasteride. LLLT is also used postoperatively after hair transplant over both the recipient and donor areas to speed up wound healing, and also this reduces pain, edema, and encourages hair growth
PRP– Platelet-rich plasma (PRP) is used to treat male and female pattern hair loss, along with minoxidil and other medical treatment.
Platelet-rich plasma is defined as a volume of the plasma fraction of autologous blood enriched with platelets at concentration 4-7 times above baseline.
The exact mechanism of how the PRP promotes hair growth is not known. The hypothesis is that growth factors released from activated platelets may stimulate the stem cells in the hair follicle bulge area for growth and differentiation via multiple molecular mechanisms.
PRP for female pattern hair loss is advised as an adjuvant therapy, not as monotherapy. The studies demonstrated that PRP with topical minoxidil is more effective than PRP alone or topical minoxidil alone.
The US FDA has not approved the PRP for the treatment of androgenetic alopecia.
Standardization of PRP preparation and injection methods may help facilitate more widespread use of PRP treatment for pattern hair loss.
EXOSOMES (Extra Cellular Vesicles-EVs)
Recently the use of exosomes in the treatment of hair loss is increasing. Their long term effect and suitability to be used as treatment modality need more extensive research and workup.
Exosomes are nano-size, extracellular, double phospholipid-layered vesicles released by most of the body’s cells with RNA, mRNA, various proteins, nucleic acids, DNA, and metabolites. The biogenesis of exosomes involves their origin in endosomes, and subsequent interactions with other intracellular vesicles and organelles generate. The size is approximately 100 nanometer.
They act as vehicles for transportation of various cellular proteins and act as a messenger between cells. The EVs have a component of the mother cell, thereby reflecting the mother cell’s properties, making them a diagnostic and therapeutic tool.
The exosomes isolated from hair follicles stem cells, both from dermal papilla and epidermal stem cells, can be used for regeneration of hair and help in revising the pathology causing the hair loss.
SMP Scalp Micropigmentation
SMP is a non-surgical option to camouflage scalp show due to thinning in female pattern hair loss and various other forms of hair loss where hair transplant is not sufficient enough to give the coverage and density. It is a form of micro-tattooing in which implantation of ink or pigment is done into the scalp skin to provide the illusion of a small hair or hair dot.
Hair Cosmetics, wigs, and hairpieces.
In advanced grades of female pattern hair loss, in alopecia totalis, and scarring alopecia, it is better to use wigs and hairpieces.
Hair Transplantation for Females
Hair transplantation in females can be considered in those who are well motivated, have realistic expectations, and who ready to take medical treatment to retain existing hair. It is also done for lowering the hairline due to a broad forehead.
Treatment of the underlying causes shall be done before hair transplantation.
Hair transplantation shall be avoided in women with diffuse thinning, including occipital area, and it is contraindicated in women with body dysmorphic disorder.
In females, hair transplantation is more challenging than in males. Following points should be considered-
Careful selection of cases with thorough counseling.
Strip is preferred in females who need a large number of grafts (up to 2000),
In smaller cases, FUE can be done.
Unshaven FUE can also be done, but it needs experience and is time-consuming.
Grafts can be implanted either by using implanters or forceps.
Recipient sites need to be created carefully in between the existing hair.
Injecting epinephrine should be avoided in the recipient area to prevent shock loss,
which is more common in females.
Most women require a smaller number of grafts from 1200 to 2000 to cover a specific area, mega sessions over 3000 grafts are rarely needed and not advisable.
Postoperative care is similar to that in men. There are more chances of shock loss, so minoxidil and medical treatment shall be started early.